Scar tissue forms in response to tissue injury after trauma. This response is mediated by multiple inflammatory pathways and involves the development of a complex matrix of collagen, hyaluronic acid, fibronectin, and proteoglycans (Salamone et al. Current Otolaryngology. McGraw Hill, 2006). Though relatively expedient, healing by scar tissue deposition (cicatrization) does not replace functional tissue by multi-germ layer regeneration.
Seventy million surgeries are performed annually in the United States, and with every surgery there is inevitable formation of scar tissue (DeFrances et al. Advance Data From Vital and Health Statistics. 2006 May; 371: 14). Fibrous adhesion formation after surgery or other trauma to tubular structures such as the esophagus, tracheobronchial tree, ureter, fallopian tubes and gut can lead to chronic illness and death. Scar tissue that forms in muscle, bone and skin tissue may lead to chronic orthopedic conditions, chronic pain, cosmetic deformity and decreased quality of life.
An example is paranasal sinus surgery. The paranasal sinuses are air spaces in the mammalian facial skeleton. These spaces can become obstructed due to various conditions such as allergy, infection, tumor, and radiation therapy. When conventional medical therapy fails, paranasal sinus surgery is a common procedure used to establish sinus drainage and to relieve the symptoms of sinus obstruction. Nearly 200,000 chronic sinus disease patients undergo sinus surgery that fails in more than 50% of cases due to unfavorable scar formation (Musy et al. American Journal of Otolaryngology. 2004 November-December; 25(6):418-22). Revision surgery has a higher complication rate than initial surgery, is less successful, and is associated with a perceived decrease in quality of life (Jiang et al. Annals of Otology, Rhinology, and Laryngology. 2002 February; 111(2):155-59).
Attempts to decrease scar tissue formation during wound healing such as with anti-inflammatory agents and inhibitors of fibroblast proliferation, are indirect and largely ineffective. These agents are non-specific, and not only inhibit fibroblasts, but also inhibit epithelial cell migration. In paranasal sinus surgery in particular, a cavity is created that must re-epithelialize with functional sinus lining (mucosa) that will promote active mucociliary clearance of sinus debris. In the treatment of tracheal stenosis, regeneration of respiratory epithelium is necessary for proper mucociliary transport and airway patency; therefore agents that inhibit re-epithelialization are counter productive to optimal healing in the paranasal sinus.
There is need for new approaches that will specifically target scar tissue without inhibiting germ layer regenerative tissue processes in order to alleviate scar tissue formation and other problems associated with medical interventions.